1jq7

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{{STRUCTURE_1jq7| PDB=1jq7 | SCENE= }}
{{STRUCTURE_1jq7| PDB=1jq7 | SCENE= }}
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'''HCMV protease dimer-interface mutant, S225Y complexed to Inhibitor BILC 408'''
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===HCMV protease dimer-interface mutant, S225Y complexed to Inhibitor BILC 408===
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==Overview==
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Biochemical studies indicate that dimerization is required for the catalytic activity of herpesvirus proteases, whereas structural studies show a complete active site in each monomer, away from the dimer interface. Here we report kinetic, biophysical and crystallographic characterizations of structure-based mutants in the dimer interface of human cytomegalovirus (HCMV) protease. Such mutations can produce a 1,700-fold reduction in the kcat while having minimal effects on the K(m). Dimer stability is not affected by these mutations, suggesting that dimerization itself is insufficient for activity. There are large changes in monomer conformation and dimer organization of the apo S225Y mutant enzyme. However, binding of an activated peptidomimetic inhibitor induced a conformation remarkably similar to the wild type protease. Our studies suggest that appropriate dimer formation may be required to indirectly stabilize the protease oxyanion hole, revealing a novel mechanism for dimerization to regulate enzyme activity.
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{{ABSTRACT_PUBMED_11524687}}
==About this Structure==
==About this Structure==
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[[Category: Herpesvirus]]
[[Category: Herpesvirus]]
[[Category: Serine protease]]
[[Category: Serine protease]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 21:37:09 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 20:37:53 2008''

Revision as of 17:37, 1 July 2008

Image:1jq7.png

Template:STRUCTURE 1jq7

HCMV protease dimer-interface mutant, S225Y complexed to Inhibitor BILC 408

Template:ABSTRACT PUBMED 11524687

About this Structure

1JQ7 is a Single protein structure of sequence from Human herpesvirus 5. Full crystallographic information is available from OCA.

Reference

Molecular mechanism for dimerization to regulate the catalytic activity of human cytomegalovirus protease., Batra R, Khayat R, Tong L, Nat Struct Biol. 2001 Sep;8(9):810-7. PMID:11524687

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